NYU Langone Health is joining a new National Institutes of Health (NIH)-sponsored program called Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) as a leading center to discover new targets for therapy in these diseases.
This effort, which is supported by $58 million in public and private funding, is an expansion of the AMP program founded in 2014, which initially focused on understanding the cellular and molecular pathways of rheumatoid arthritis and systemic lupus erythematosus (SLE), and now is being expanded to include psoriatic disease (which includes psoriasis and psoriatic arthritis) and Sjogren's syndrome (also called Sjogren's disease).
The partnership will pair rheumatologists, dermatologists, nephrologists, immunologists, and computational and systems biologists from NYU Langone and several other academic centers across the United States with the NIH, the U.S. Food and Drug Administration (FDA), pharmaceutical companies, and nonprofit organizations. Jill P. Buyon, MD, the Sir Deryck and Lady Va Maughan Professor of Rheumatology in the Department of Medicine, will serve as contact principal investigator of the AMP AIM program's lupus team. Jose U. Scher, MD, the Steere-Abramson Associate Professor, will lead the program's microbiome core and serve as co-principal investigator of a psoriatic disease clinical team, and Peter M. Izmirly, MD, associate professor of medicine, will oversee a clinical site for the Sjogren's disease team.
The Division of Rheumatology has a proven record of excellence in research and clinical care. As leaders in this nationwide endeavor, we now have an opportunity to bring our world-class researchers to the forefront of the fight against autoimmune and inflammatory diseases."
Steven B. Abramson, MD, executive vice president and vice dean for education, faculty, and academic affairs, chief academic officer at NYU Langone and chair of NYU Grossman School of Medicine's Department of Medicine
An acceleration of discoveries in lupus research
Dr. Buyon's group in the new AMP AIM program, LOCKIT (Lupus Omics Cutaneous Kidney Investigation Team), is a partnership with Johns Hopkins University, The Ohio State University, and the University of Pennsylvania. This leadership team will also be bolstered by additional sites including Albert Einstein College of Medicine, the University of California, San Francisco, Brigham and Women's Hospital, the University of Michigan, the University of Rochester, and the University of Texas Southwestern. These institutions' established patient registries will be leveraged to address molecular underpins of early kidney disease, refractory lupus nephritis, and a spectrum of cutaneous diseases with the hope of bringing new therapies to patients.
"As the pace of discovery in the biology, genetics, and environmental regulation of systemic lupus erythematosus accelerates, the speed and efficiency of translationally applying that research to clinical care assumes even greater importance," Dr. Buyon says. "We now have an unprecedented opportunity to harness technological advances to deconstruct and reconstruct the enormity of phenotypic and immunologic heterogeneity in this prototypic autoimmune disease."
NYU Grossman School of Medicine's Division of Rheumatology led one of the lupus disease teams for the earlier AMP program that paved the way for the now-expanded effort. The SLE team's focus on lupus nephritis, aided by an enrollment of more than 150 patients at NYU Langone who contributed kidney tissue for research, helped establish that biopsies are safe. The team developed new protocols for tissue preservation and dissociation and set the stage for transcriptomic evaluation of single cells. This work has already identified new cell clusters and pathways that may lead to novel therapies and identified that accessible tissue such as the skin may hold clues to kidney disease.
Probing the microbiome and skin for clues
The AMP AIM program's microbiome core, called Micro-TeACH (Microbiome Technology and Analytic Center Hub), led by Dr. Scher, will incorporate intestinal, skin, and other tissue-related microbiome features to aid in the pathogenetic reconstruction for various autoimmune and immune-mediated diseases. Micro-TeACH is a New York City-based hub and will expand a decade-long collaboration with the Clemente Lab Icahn Icahn School of Medicine at Mount Sinai.
The hub will help researchers interrogate the gut microbiome and its potential metabolic capacity to modulate antirheumatic drugs' pharmacokinetics and response to therapy. In addition, the tools will enable an integration of the cutaneous and oral microbiome with tissue-derived spatial transcriptomics and single-cell technologies to better understand the triggers of inflammation and autoimmunity.
The psoriatic disease team Dr. Scher is also co-leading has been dubbed ELLIPSS (Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium) and is a coalition of dermatologists, rheumatologists, immunologists, and epidemiologists from the University of Rochester, University of Michigan, University of California, San Francisco, and University of Pennsylvania. Participants in ELLIPSS with varying stages of psoriatic disease will have biopsies of the skin and joint synovium to better identify the distinct functional or pathobiological mechanisms.
"The skin may have the code for who progresses, why, and how," Dr. Scher says. "We want to find which cells that reside in the skin are being attracted—the term we use is homing—to the joints and produce and promote inflammation there."
Any patterns and pathways, in turn, could have major implications for therapeutics. "What's in that code may help us adopt a desperately needed precision medicine approach," Dr. Scher says.
Interrogating the tissue and systems biology of Sjogren's disease
STAMP (the Sjogren's Team for Accelerating Medicines Partnership), led by Dr. Caroline Shiboski at the University of California, San Francisco, is strategically positioned to apply cutting-edge technologies to interrogate the tissue and systems biology of Sjogren's disease. Dr. Izmirly will join the team and recruit subjects from NYU Langone's large outpatient practice, with a focus on those with both lupus and Sjogren's disease.
Sjogren's disease is a common systemic autoimmune rheumatic disorder second only to rheumatoid arthritis in prevalence. There are very few therapeutic options for patients outside of symptom management, so there is a need for better understanding of the pathogenetic mechanisms of disease. The STAMP group is positioned to further this goal, designing clinical research protocols to recruit, enroll, phenotype, and collect relevant biospecimens from observational cohorts of people with Sjogren's disease and controls.
"We have expertise in rheumatology, oral health, and ophthalmology, and will perform full recruitments of these subjects using the best practices established by the STAMP group," says Dr. Izmirly. "By standardizing these protocols, we will be in a position to better understand the pathogenesis of Sjogren's disease and the mechanisms of the disease's progression, which will allow us to identify therapeutic targets and new biomarkers."
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